Balakrishnan S, Bhargava V K, Pandhi P
Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Methods Find Exp Clin Pharmacol. 1999 Jul-Aug;21(6):441-7. doi: 10.1358/mf.1999.21.6.541926.
The effect of nitrendipine (NTP) alone and in combination with phenytoin (PHT) and valproate (VPA) against maximal electroshock seizures (MES) was studied in rats. In addition, the psychomotor effects of NTP alone and in combination with PHT and VPA were evaluated using the following tests: a) rotarod performance; b) spontaneous motor activity; c) despair behavior; d) righting reflex; e) hole board test; and f) passive avoidance test. ED50 values of PHT, VPA and NTP were 13,255 and 3.6 mg/kg, respectively. When NTP was combined with PHT or VPA, the ED50 values decreased to 0.9 and 226 mg/kg, respectively. In the psychomotor function tests, for the same degree of protection (50%) afforded against MES, PHT or VPA produced a greater impairment in all the parameters compared to NTP alone or a combination of NTP with PHT or VPA. Furthermore, NTP reversed the depression and long-term memory loss induced by PHT and VPA. Thus, NTP was effective against MES in rats, potentiating the anti-electroshock activity of PHT and VPA and producing less impairment of psychomotor activity. Thus, the agent can be considered a potential antiepileptic warranting further studies.
在大鼠中研究了尼群地平(NTP)单独以及与苯妥英(PHT)和丙戊酸盐(VPA)联合使用对最大电休克惊厥(MES)的影响。此外,使用以下试验评估了NTP单独以及与PHT和VPA联合使用时的精神运动效应:a)转棒试验;b)自发运动活动;c)绝望行为;d)翻正反射;e)洞板试验;f)被动回避试验。PHT、VPA和NTP的半数有效剂量(ED50)值分别为13、255和3.6mg/kg。当NTP与PHT或VPA联合使用时,ED50值分别降至0.9和226mg/kg。在精神运动功能试验中,对于给予MES同等程度的保护(50%),与单独使用NTP或NTP与PHT或VPA联合使用相比,PHT或VPA在所有参数上产生了更大的损害。此外,NTP逆转了由PHT和VPA引起的抑郁和长期记忆丧失。因此,NTP对大鼠的MES有效,增强了PHT和VPA的抗电休克活性,并且对精神运动活动的损害较小。因此,该药物可被认为是一种有潜力的抗癫痫药物,值得进一步研究。